The somatotropinergic system (STS) is the only neuroendocrine axis in which specific stimulatory and inhibitory neuropeptidergic regulators have been demonstrated thus far. In normal conditions, growth hormone-releasing factor (GRF) and somatostatin (SS) are the hypothalamic hypophysiotropic hormones responsible for the regulation cf growth hormone (GH) secretion.
At the same time, GRF and SS are influenced by central monoaminergic and peptidergic neuromodulators to optimize the functioning of the STS. See Cacabelos R., Niigawa H., Hariguchi S. "Hypothalamohypophyseal system and brain function." J. Clin. Sci. 22:1108-1120 (1986). Recent investigations suggest that the functional structure of the STS characteristically represented at the peripheral level might exist in the central nervous system (CNS). Furthermore, SS levels are reduced in specific areas of the CNS in patients with senile dementia and are elevated in the neostriatum of patients with Huntington's chorea. See Cacabelos R., Niigawa H., Ikemura Y." Neuroendocrine correlates in senile dementia of the Alzheimer type. "Progr. Clin. Neurosci. 2:231-247 (1986); Beal M. F., Uhl G., Mazurek M. F., Kowall N., Martin J. B. "Somatostatin: Alterations in the central nervous system in neurological diseases." in: Martin J. B., Barchas J. D., Ed. Neuropeptides in neurologic and psychiatric disease. pp. 215-257 (Raven Press, New York, 1986); Epelbaum J. "Somatostatin in the central nervous system: physiology and pathological modifications." Progr. Neurobiol. 27:63-100 (1986). In addition, an abnormal rise of GH in response to GnRH or TRH has been described in several neuropsychiatric disorders. See in Brown G. M., Koslow S. M., Reichiin S. Ed. Neuroendocrinology and psychiatric disorder (Raven Press, New York 1984) It has been speculated that the central regulators of the STS (e.g., GRF, SS) influence higher activities of the CNS. Such speculation led to search for potential therapeutic uses of these neuropeptides in those neurological diseases in which the normal functioning of the STS is impaired.
The neurochemical characteristics of early and late onset senile dementia of the Alzheimer type (SDAT) can be clearly demonstrated in postmortem studies in which it is possible to observe that cholinergic and somatostatinergic deficits are more pronounced in patients with an early onset of the disease. See Rossor M. N., Iversen L. L., Reynolds G. P., Mountjoy C. Q., Roth M. "Neurochemical characteristics of early and late onset types of Alzheimer's disease." Br. Med. J. 288:961-964 (1984). In advanced stages, clinical assessments show that the course of the disease is more rapid and prominent in younger patients.
Since dementia may be attributed to various etiologies of which SDAT accounts for at least 50% of the cases, the search for antemortem markers capable of establishing an early differential diagnosis for identifying potentially reversible or treatable causes of dementia is becoming an extremely important matter.
SDAT is believed to be a multisystem disorder. See Price D. L., Struble R. G., Whitehouse P. J., Kitt C. A., Cork L. C., Walker L. C., Casanova M. F. "Alzheimer's disease: A multisystem disorder." in: Martin J. B., Barchas J. D., (Ed). Neuropeptides in neurologic and psychiatric disease. pp. 209-214 (Raven Press, New York 1986) The most relevant peptidergic abnormalities in SDAT involve a clear deficit in cortical somatostatin and corticotropin-releasing factor (CRF). Other peptidergic and monoaminergic systems are also affected.